In anesthetized man, general anesthetic agents dilate peripheral blood vessels and depress their responsiveness to adrenergic stimuli. The overall aim of the proposed research is to investigate the mechanism of action of the volatile inhalation agent halothane, and the neuroleptic intravenous agent droperidol on vascular smooth muscle. Based on recent literature references and on preliminary work by the investigator it is postulated that halothane's vascular effect may be the result of inhibition of the release of adrenergic transmitter from postganglionic terminals in vessel walls. This possibility will be examined in isolated venous and arterial preparations whose nerve endings have been pre-loaded with 3H-NE. The efflux of 3H-NE and its metabolites will be followed in control conditions and during exposure to clinically used concentrations of halothane. The alternate hypothesis, that halothane has a direct depressant action on vascular smooth muscle, will also be examined. As an extension to the studies with halothane it is proposed to examine the action of droperidol on adrenergic transmission in isolated vascular smooth muscle using 3H-NE. Patients anesthetized with this compound often become hypotensive, an effect originally thought due to alpha receptor blockade. However, recent reports indicate that droperidol occasionally causes vaso-constriction and hypertension. Clarification of the role of these two anesthetic drugs on adrenergic transmitter release in vascular smooth muscle is highly desirable at this time not only to achieve a better understanding of their mechanism of action but because knowledge of these mechanisms is the key to more rational therapy to reverse circulatory depression with these agents.